DESCRIPTION (Abstract of the application) Recent advances in genomic technologies have made possible the simultaneous examination of the expression patterns of a large number of genes in many biological systems. The principal approach, often called the "chip technology" involves the production of high-density arrays (microarrays) that contain thousands of previously isolated complementary DNA (cDNA) sequences and which are used to analyze gene expression on a global scale. The potential for gaining important and novel information on the fundamental mechanisms of biology and pathobiology with this technology is enormous. Our group is a consortium of investigators who are studying the biology-and pathobiology of the endocrine, renal or gastrointestinal system. To ensure that our research benefits from the power of rapidly advancing genomic techniques, we propose to form the Hopkins DK Center for the Analysis of Gene Expression. The Goals of this research application are (1) to perform genome-wide patterning of gene expression for the involved projects using cDNA microarrays, and (2) to establish a potentially important and powerful thematic approach to the analysis of gene expression among the concerned projects. The Specific Aim is to establish a core research facility at the Johns Hopkins University School of Medicine to support the production of cDNA microarrays and the analysis of gene profiles for investigators whose research is based on areas within the scientific mission of the NIDDK. The initial phase of the grant application will include 15 projects from established investigators and 7 pilot/feasibility projects from junior investigators. These projects share a programmatic emphasis on research that is focused on the molecular regulatory mechanisms in the biology and pathobiology of the renal, digestive, and endocrine organs. The projects can further be divided into 3 major themes that include: (1) The genomic responses to stress or inflammation, (2) Mechanisms regulating the proliferative and/or differentiated phenotype in epithelial cells, and (3) Cellular and molecular dysfunction in diabetes and other metabolic/endocrine disorders. The analysis of the array data will be supported by a Bioinformatics and a Biostatistics Core, staffed by local experts in the respective field. Thus, this application represents a rational and focused approach to the specific questions that each investigator addresses. The potential for gaining novel and relevant insights into the molecular mechanisms responsible for each of the three main themes of the proposed research through the use of the DK Center by the participating investigators is considerable.